The following projects will be investigated during the next year of support. (1) Development of a double-barrelled electrode capable of measuring intracellular p02 and pH. These electrodes will be constructed and calibrated for penetration and measurement in large neurons. Experimentally, the electrodes produced will be tested in rat brain for measurement of intracellular pH in two conditions: normal (lightly anesthesized) and brief hypoxia. (2) Continue development of the multicomponent, heterogeneous, random walk model for molecular transport. This program currently models transport from within the capillary to the neuron and transport within the neuron. Presently, the model includes oxygen, glucose, and lactate transport. The per cent metabolism and the ATP generation has been added to the simulation and will be incorporated during the year. (3) The rheological and biochemical aspects of the clotting mechanism, particularly the role of factors such as protein C, will be completed. A kinetic analysis of possible production and utilization mechanisms will be determined using past results and new modeling techniques. (4) Modeling of oxygen consumption in Krogh cylinder models will be continued. In addition, a lumped parameter modeling technique will be initiated with the direct purpose of identifying and correlating oxygen transport during experimental hypoxia. (5) A model for transport of hydrogen ions will be developed. With the capability of measuring intracellular pH and the apparent relationship between cell death and cummulative pH, this model will be used to substantiate experimental data and predict neuron death.